Since 1982, investigators from the Radiation Epidemiology Branch (REB), NCI and the University of Minnesota have been following a large, mostly female (73%), cohort of U.S. radiologic technologists for the purpose of evaluating and quantifying carcinogenic risks of chronic moderate- to low-dose radiation exposures. The cohort offers important advantages over other occupational radiation cohorts, including validated cancer incidence outcomes, comprehensive covariate data, and a large female membership, which affords a rare opportunity to study low-dose effects on the breast and thyroid in women. Recent analyses using relatively crude exposure indices revealed significantly elevated risks for certain cancers (e.g., breast, leukemia, non-melanoma skin, melanoma, thyroid) associated with working in the earlier calendar years, when occupational radiation exposures were likely high. Estimates of annual radiation doses for individual radiologic technologists have been developed in collaboration with the National Institute for Occupational Safety and Health, as well as records from a commercial dosimetry company, Landauer, Inc. Detailed statistical modeling and review of the literature on historical exposures is largely complete. Preliminary dose estimates are available and a refined version will be ready in 2003. More than 1,500 biospecimen samples have been collected from primarily breast and thyroid cancer cases and controls. Analyses are underway for polymorphic variants in candidate breast cancer susceptibility genes and DNA repair genes, as well as functional studies in lymphoblastoid cell lines. A cohort of 20,000 Mayak nuclear facility workers (in the former Soviet Union)is being studied because they comprise a unique occupational group for protracted exposure to external radiation at high doses and exposure to plutonium. Mortality analyses of the Mayak workers demonstrate that internal exposure to plutonium results in excess risk of lung, liver and bone cancers, with higher risks for females than males. Analyses evaluating the efects of external radiation exposure showed dose-response relationships for leukemia and for solid cancers. A cohort of about 30,000 persons who lived downstream of the Mayak plant is also being studied because of exposure to large releases of radioactive wastes into the Techa River that resulted in both external exposure and exposure to strontium. Dose-response relationships have been demonstrated for both leukemia and solid cancers. For both cohorts, dosimetry is being improved to allow more precise quantification of dose-response relationships. Several studies of Chornobyl clean-up workers are currently underway. Cancer incidence through 1998 is being evaluated in three cohorts, comprising 17,000 clean-up workers, from Estonia, Latvia, and Lithuania who were sent to Chornobyl (Ukraine) following the reactor accident in 1986. Cohort members are interviewed to elicit other risk factor information. In addition, with support from DOE and NRC, NCI is conducting a "nested" study of leukemia and other hematologic disease among the Chornobyl clean-up workers in Ukraine. A cancer incidence study is planned to determine whether female flight attendants are at increased risk of breast or other cancers due to cosmic radiation exposure. A biodosimetry study to assess cosmic radiation exposure will compare the induction and persistence of chromosome aberrations by fluorescence in situ hybridization (FISH) among 81 pilots and 50 university faculty with minimal flying experience.